The Role of Serotonin in Energy Homeostasis in C. elegans

描述（由申请人提供）： 为了确保生存，动物必须不断评估环境中的食物状况，并通过将食物摄入量与能量消耗相匹配来做出适当的反应。两者之间的净平衡反映在动物的脂肪储存中。神经递质5-羟色胺在维持这种动态平衡中起着核心作用，通过传递来自环境的食物信号来引起动物行为和生理的变化，从而维持脂肪稳态。这项研究的目的是解决这个问题：“血清素信号是如何调节C。elegans？“我已经确定了一些关键基因，这些基因对C.优雅使用行为和生理分析的组合，我将研究这些新发现的基因在食物摄入和能量消耗中的作用。结合分子和遗传分析，我的目标是详细说明食物感觉与摄食调节和能量消耗变化之间的关系。优雅我目前的研究目标与我对了解环境如何在生物体水平上影响复杂行为和生理的长期兴趣是一致的。了解遗传学和环境的复杂交叉是生物科学的前沿，对人类健康有着重大的直接影响。这里提出的工作奠定了基础，我将开始作为一个独立的研究人员在学术研究机构在未来两年。我目前在加州大学旧金山分校弗朗西斯科的环境下，由Kaveh Ashrafi博士和基思山本博士指导，非常适合我的科学和专业兴趣。能量平衡失调导致肥胖，这是一个全球范围内日益严重的健康问题。事实上，目前的估计表明，超过30%的美国人肥胖，这是心血管疾病，糖尿病和预期寿命缩短的主要风险因素。在包括小鼠和人类在内的许多物种中，血清素功能的古老保守性表明，本文提出的工作将为体脂调节的研究提供新的遗传靶点。

DESCRIPTION (provided by applicant): To ensure survival, animals must constantly assess food status in the environment, and respond appropriately by matching food intake to energy expenditure. The net balance between the two is reflected in the fat stores of the animal. The neurotransmitter serotonin plays a central role in maintaining this dynamic balance, by relaying food signals from the environment to elicit changes in behavior and physiology of the animal so that fat homeostasis is maintained. The goal of the research proposed here is to address the question: "How does serotonin signaling modulate energy balance in C. elegans?" I have identified a few key genes that are important for serotonin fat regulation in C. elegans. Using a combination of behavioral and physiological assays, I will examine the roles of these newly-identified genes in food intake and energy expenditure. Together with molecular and genetic analyses, I aim to specify the serotonergic network that couples food sensation to changes in feeding regulation and energy expenditure in C. elegans. My current research objectives are well-aligned with my long-term interest in understanding how the environment influences complex behavior and physiology at the organismal level. Understanding the complex intersection of genetics and environment is a frontier in the biological sciences with major, direct impacts on human health. The work proposed here lays the foundation upon which I will embark as an independent investigator at an academic research institution in the next two years. My current environment at the University of California-San Francisco under the mentorship of Dr. Kaveh Ashrafi and Dr. Keith Yamamoto, is ideally suited for my scientific and professional interests. The de-regulation of energy balance leads to obesity, a rising health concern world-wide. Indeed, current estimates suggest that more than 30% of Americans are obese, a condition that is a prime risk factor for cardiovascular disease, diabetes and reduced life expectancy. The ancient conservation of serotonin function in many species including mice and humans suggests that work proposed here will provide novel genetic targets for the study of body fat regulation.